1. Field of the invention
This invention relates to a vaccine against bacteria of the genus Pasteurella, especially Pasteurella haemolytica, which is the organism responsible for pasteurellosis in sheep and one of those responsible for pasteurellosis in cattle, and Pasteurella multocida, which is another responsible for pasteurellosis in cattle.
2. Description of prior art
Pasteurellosis is a common respiratory disease of sheep and cattle which may often lead to fatality, particularly in the case of young animals, and thus the prevention and control of this disease is of great importance to farmers engaged in the rearing of sheep and cattle. In sheep the disease appears as either a pneumonia or a septicaemic condition dependent upon the age of the infected animal and the strain of the infecting organism, whereas in cattle the disease is encountered primarily as a pneumonia in regions with temperate climates. Two biotypes of P. haemolytica have been identified, the A biotype generally associated with septicaemias in young lambs and pneumonias in older sheep, and the T biotype generally associated with septicaemias in adult sheep, and within these two biotypes fifteen different serotypes (eleven "A" and four "T" serotypes) have been identified. Serotype A2 is particularly important in relation to sheep and A1 in relation to cattle.
It has been a problem to improve the antigenicity of commercial vaccines against pasteurellosis. The sheep vaccines comprise various strains of P. haemolytica, representing the more important of the biotypes and subtypes thereof. Cattle vaccines also comprise P. multocida.
European Patent Specification 36995A (Norden Labs.) describes a live vaccine of Pasteurella haemolytica and multocida, attenuated to make them less pathogenic by culturing them in broth containing an acridinium compound.
In UK Patent Specification 2023420A (Hoechst UK) a vaccine against Pasteurella haemolytica contains antigens said to be associated with the capsule of the bacterium. An extract of such antigens is prepared by heating and centrifuging the culture and collecting the supernatant. The precipitated cells are sterilised and washed. Both the supernatant and the washed cells are included in the vaccine.
French Patent Specification 2182909A (Wellcome) or the corresponding UK Specification 1441098 describe a vaccine component prepared from P. haemolytica or multocida by extracting a whole cell structure, lysate, or cell-free culture medium with a lower alkanol or lower alkyl ketone or "salting out" with a salt such as ammonium sulphate to precipitate endotoxin. Endotoxin is a lipopolysaccharide component present in the capsule of the organism. The endotoxin-free supernatant re-treated with the solvent or salt (as before) at a high concentration, to precipitate the antigenic substance for use as a vaccine component.
Another attempt at improvement is described in U.S. Pat. No. 4,346,074, or its European equivalent 20356B (National Research Development Corporation) or its British equivalent 2029219A (Gilmour et al.). These patents relate to a vaccine comprising as essential components capsular extract, especially sodium salicylate extract, of the A1 serotype in combination with heat-killed cells of the A2 serotype. In the extraction process, the bacterial cells are centrifuged, shaken in sodium salicylate solution and then re-centrifuged and the supernatant concentrated by dialysis.
For a recent review of vaccination against pasteurellosis, see N. Gilmour and N. Donachie in "Science and Quality Lamb Production" (Agricultural and Food Research Council, UK, 1986) pages 22, 23 and 28.
Additional prior art is referred to after the "Summary of the invention", without which its context would not be clear.